1. South Asian medical cohorts reveal strong founder effects and high rates of homozygosity
- Author
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Jeffrey D. Wall, J. Fah Sathirapongsasuti, Ravi Gupta, Asif Rasheed, Radha Venkatesan, Saurabh Belsare, Ramesh Menon, Sameer Phalke, Anuradha Mittal, John Fang, Deepak Tanneeru, Manjari Deshmukh, Akshi Bassi, Jacqueline Robinson, Ruchi Chaudhary, Sakthivel Murugan, Zameer ul-Asar, Imran Saleem, Unzila Ishtiaq, Areej Fatima, Saqib Shafi Sheikh, Shahid Hameed, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-ur-Rehman Memon, Anjum Jalal, Shahid Abbas, Philippe Frossard, Christian Fuchsberger, Lukas Forer, Sebastian Schoenherr, Qixin Bei, Tushar Bhangale, Jennifer Tom, Santosh Gopi Krishna Gadde, Priya B V, Naveen Kumar Naik, Minxian Wang, Pui-Yan Kwok, Amit V. Khera, B. R. Lakshmi, Adam S. Butterworth, Rajiv Chowdhury, John Danesh, Emanuele di Angelantonio, Aliya Naheed, Vinay Goyal, Rukmini M. Kandadai, Hrishikesh Kumar, Rupam Borgohain, Adreesh Mukherjee, Pettarusp M. Wadia, Ravi Yadav, Soaham Desai, Niraj Kumar, Atanu Biswas, Pramod Kumar Pal, Uday B. Muthane, Shymal K. Das, Vedam L. Ramprasad, Prashanth L. Kukkle, Somasekar Seshagiri, Sekar Kathiresan, Arkasubhra Ghosh, V. Mohan, Danish Saleheen, Eric W. Stawiski, and Andrew S. Peterson
- Subjects
Science - Abstract
Abstract The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.
- Published
- 2023
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